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Verbal Fluency in Parkinson`s disease: neuroanatomical correlates and functional networks modulated by noninvasive brain stimulation

  • Autores: Joana Braga Pereira
  • Directores de la Tesis: David Bartrés Faz (dir. tes.), Carme Junqué i Plaja (dir. tes.)
  • Lectura: En la Universitat de Barcelona ( España ) en 2012
  • Idioma: inglés
  • Tribunal Calificador de la Tesis: Isidro Ferrer Abizanda (presid.), Javier Pagonabarraga Mora (secret.), Cristina Sánchez Castañeda (voc.)
  • Materias:
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  • Resumen
    • Parkinson’s disease (PD) is currently the second most common neurodegenerative disorder after Alzheimer’s disease (AD), affecting 100.000 people in Spain and more than 4 million people worldwide. Being a movement disorder, impairment of motor functions is considered to be the hallmark symptom of PD. However, cognitive dysfunction is now recognized as a common feature, being present since early disease stages and affecting the majority of patients as the disease progresses. In line with this, one of the most common cognitive deficits found in PD patients are verbal semantic and phonemic fluency deficits. Although there are still no established biomarkers for PD, neuroimaging methods offer the possibility of mapping the neurobiological substrates of motor and cognitive impairment in these patients. Amongst the available neuroimaging techniques, structural and functional magnetic resonance imaging (MRI, fMRI) produces images of the brain that provide quantitative values of cerebral atrophy and brain dysfunction, respectively. These techniques are relevant because they shed light into neurodegeneration processes occurring in PD compared to normal aging as well as those pathological processes that specifically underlie cognitive decline in these patients. In addition to neuroimaging, another method that allows studying brain networks and their disruption in PD is transcranial direct current stimulation (tDCS), which, in addition to modulating functional connectivity, provides a tool for cognitive and motor rehabilitation. This thesis comprises three different studies that had two main goals. On one hand, it was aimed at characterizing the brain’s structural and functional correlates of semantic and phonemic fluency cognitive deficits in patients with PD using MRI, fMRI and tDCS methods. On the other hand, given the lack of a comparison of the relative contribution of different existing MRI-based techniques to characterize cortical degeneration in PD, specific changes in different characteristics of the cortical gray matter (GM) layer were assessed to determine whether brain atrophy in PD can be attributed to changes in cortical thickness, cortical folding or GM volume. The first study of this thesis showed that semantic fluency is associated with GM density in cortical frontal and temporal areas in PD patients, suggesting this function relies both on executive functions and semantic memory processes. The second study showed that by stimulating the left dorsolateral prefrontal cortex with tDCS, significant enhancement of functional connectivity occurs in both semantic and phonemic fluency networks in PD, in addition to a significant improvement of phonemic fluency functions. The third and final study showed that amongst the most widely used neuroimaging analysis techniques to assess cortical changes in PD, cortical thickness seems to be the most sensitive, followed by cortical folding and finally GM volume as assessed by voxel-based morphometry. To conclude, the results that were found in this thesis shaded light into previously unstudied issues related to PD, increasing the knowledge on some of the cerebral pathological changes that affect patients with this disorder. In addition they encourage the use of tDCS to explore brain networks in PD and suggest that surface-based techniques such as cortical thickness are useful to assess GM changes occurring in these patients.


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